Gene therapy for mitochondrial disorders
In this review, we detail the current state of application of gene therapy to primary mitochondrial disorders (PMDs). Recombinant adeno-associated virus-based (rAAV) gene replacement approaches for nuclear gene disorders have been undertaken successfully in more than ten preclinical mouse models of PMDs which has been made possible by the development of novel rAAV technologies that achieve more efficient organ targeting. So far, however, the greatest progress has been made for Leber Hereditary…
Pearls & Oy-sters: Leber Hereditary Optic Neuropathy-Plus Masquerading as Neuromyelitis Optica Spectrum Disorder in a 2-Year-Old Child
“Leber hereditary optic neuropathy (LHON-Plus)” is a phenotype of LHON that is characterized by extraocular neurologic manifestations, which may be the first manifestations of the disease.
The genetic puzzle of a SOD1-patient with ocular ptosis and a motor neuron disease: a case report
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71 years-old man diagnosed with ALS with atypical clinical features consisting in progressive ocular ptosis and sensorineural deafness. Genetic analyses revealed two heterozygous variants, in the SOD1 (OMIM*147450) and the TBK1 (OMIM*604834) genes respectively, and furthermore mitochondrial DNA…
DNAJC30 Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients
Leber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial DNA. Recently, an autosomal recessive form of LHON (LHONAR1, arLHON) has been discovered, caused by biallelic variants in the DNAJC30 gene. This study provides the results of the DNAJC30 gene analysis…
Clinically Diagnosed Occult Macular Dystrophy Habouring an m.14502T>C Mitochondrial DNA Mutation Associated with Leber’s Hereditary Optic Neuropathy: Case Report and Literature Review
A 29-year-old female with no family history presented with bilateral progressive blurred vision. Her symptoms appeared at 12-years-old and her visual acuity had since deteriorated from 0.6 to 0.2 bilaterally with decreased critical flicker frequency and bilateral central scotomas. She did not have a relative afferent pupillary defect. Fundoscopy revealed no distinct disc hyperaemia, atrophy, or peripapillary telangiectatic vessels. The retinal nerve fibre layer appeared normal on optical…
Leber hereditary optic neuropathy gene therapy
PURPOSE OF REVIEW: To discuss relevant clinical outcomes, challenges, and future opportunities of gene therapy in Leber hereditary optic neuropathy (LHON).
Case report: Mutations in DNAJC30 causing autosomal recessive Leber hereditary optic neuropathy are common amongst Eastern European individuals
CONCLUSION: This finding adds to the growing cohort of patients with arLHON and demonstrates the importance of DNAJC30 screening in patients with molecularly undiagnosed LHON, particularly in Eastern European individuals. It is of heightened translational significance as patients diagnosed with arLHON exhibit a better prognosis and response to therapeutic treatment with the co-enzyme Q10 analog idebenone.
Correlation Between Residual Sensitivity in the Central Inferior Nasal Visual Field and Visual Function in Chronic Leber Hereditary Optic Neuropathy patients
CONCLUSIONS: Patients with chronic LHON tended to retain the sensitivity detectable with the size V stimulus at the central inferior nasal visual field regions, where the fixation ellipse fell. Visual acuity, which influences daily activity, was spatially correlated with residual visual sensitivity.
Mitochondrially Targeted Gene Therapy Rescues Visual Loss in a Mouse Model of Leber’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is a common mitochondrial genetic disease, causing irreversible blindness in young individuals. Current treatments are inadequate, and there is no definitive cure. This study evaluates the effectiveness of delivering wildtype human NADH ubiquinone oxidoreductase subunit 4 (hND4) gene using mito-targeted AAV(MTSAAV) to rescue LHOH mice. We observed a declining pattern in electroretinograms amplitudes as mice aged across all groups (p
Exploring mito-nuclear genetic factors in Leber’s hereditary optic neuropathy: insights from comprehensive profiling of unique cases
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial complex I disorder and causes inexorable painless vision loss. Recent studies from India reported that a significant proportion of LHON patients lack primary mitochondrial DNA mutations, suggesting that alternative genetic factors contribute to disease development. Therefore, this study investigated the genetic profile of LHON-affected individuals in order to understand the role of mito-nuclear genetic factors in LHON. A total of…